Quantitative imaging biomarkers: Effect of sample size and bias on confidence interval coverage
Quantitative imaging biomarkers: Effect of sample size and bias on confidence interval coverage
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DOI：
10.1177/0962280217693662
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发表时间：
2018-10-01
影响因子：
2.3
通讯作者：
Bullen, Jennifer
中科院分区：
文献类型：
--
作者：
Obuchowski, Nancy A.;Bullen, Jennifer
定量成像生物标志物（QIB）越来越多地用于医疗实践和临床试验。采用定量成像生物标志物的重要第一步是通过一项或多项性能研究表征其技术性能，即精度和偏倚。然后，给定技术性能，可以构建新患者的真实生物标志物值的置信区间。估计偏差和精度可能是有问题的，因为很少都估计在同一项研究中，精度的研究通常是相当小的，和偏差不能测量时，没有参考standard.Methods一个蒙特卡罗模拟研究进行评估的因素，影响标称覆盖范围的置信区间为一个新的病人的定量成像生物标志物的测量和定量成像生物标志物随时间的变化。考虑的因素包括估计偏差和精密度，固定和非比例偏差的影响，聚类数据，和没有一个参考standard.Results技术性能研究的定量成像生物标志物的样本量应包括至少35个重测科目，以估计精度和65例估计偏差。在无偏倚假设下构建的新患者定量成像生物标志物测量的置信区间提供标称覆盖范围，只要固定偏倚
Introduction Quantitative imaging biomarkers (QIBs) are being increasingly used in medical practice and clinical trials. An essential first step in the adoption of a quantitative imaging biomarker is the characterization of its technical performance, i.e. precision and bias, through one or more performance studies. Then, given the technical performance, a confidence interval for a new patient's true biomarker value can be constructed. Estimating bias and precision can be problematic because rarely are both estimated in the same study, precision studies are usually quite small, and bias cannot be measured when there is no reference standard.Methods A Monte Carlo simulation study was conducted to assess factors affecting nominal coverage of confidence intervals for a new patient's quantitative imaging biomarker measurement and for change in the quantitative imaging biomarker over time. Factors considered include sample size for estimating bias and precision, effect of fixed and non-proportional bias, clustered data, and absence of a reference standard.Results Technical performance studies of a quantitative imaging biomarker should include at least 35 test-retest subjects to estimate precision and 65 cases to estimate bias. Confidence intervals for a new patient's quantitative imaging biomarker measurement constructed under the no-bias assumption provide nominal coverage as long as the fixed bias is